An understanding of the cellular control of lipid metabolism continues to be a challenging and fundamental problem of molecular biology and has many biomedical implications. The cellular mechanisms associated with the regulation of fatty acid synthesis are not completely understood. In addition to the availability of substrates, the control at the enzymatic level could be expressed by the control of activity of enzymes by the regulators. In the present studies, we have determined the effect of malonyl CoA on the activity of fatty acid synthetase. Malonyl CoA irreversibly inhibits fatty acid synthetase. Malonyl CoA irreversibly inhibits fatty acid synthetase and the rate and extent of inhibition is dependent upon malonyl CoA/enzyme ratios rather than the absolute concentrations. At concentrations lower than that of malonyl CoA, acetyl CoA promotes inactivation whereas at higher concentrations, it has protective effects. NADP, the oxidised form of the coenzyme NADPH, also shows protective effects. These studies have been related to the alteration of conformation around the condensing site of fatty acid synthetase. Other studies have included the effect of insulin and triiodothyronine on the control of biosynthesis of fatty acid synthetase.